Is TP53 p.Ala355= (c.1065T>C) pathogenic?

TP53 p.Ala355= (c.1065T>C) is classified Likely benign in TP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-09-23). Absent from gnomAD v4.1.

How common is TP53 p.Ala355= (c.1065T>C) in the general population?

TP53 p.Ala355= (c.1065T>C) is absent from gnomAD v4.1 (gnomAD).

TP53 p.Ala355=

c.1065T>C · rs1057523467 · VCV389554

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.43	GERP 2
Overall
CADD	8.425	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TP53
Protein: p.Ala355=
Coding: c.1065T>C
MANE Select: NM_000546
dbSNP: rs1057523467
Type: single nucleotide variant
Location: chr17:7670644 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 355: the 'interaction with carm1' region; a turn; the 'interaction with hipk2' region; the 'oligomerization' region; the 'disordered' region; the 'interaction with hipk1' region

Full TP53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TP53 p.Ala355Asp Uncertain significance ★★ ⚠ same residue
TP53 p.Ala355Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ala355Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ala355Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ala355Val Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ala355fs Uncertain significance ★ same residue
TP53 c.375+5G>A Likely pathogenic ★★★ same type
TP53 c.919+1G>A Pathogenic ★★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/tp53-p-ala355 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown